Encoded beads having oligonucleotides attached and formed in arrays

Abstract

A method and apparatus for the manipulation of colloidal particulates and biomolecules at the interface between an insulating electrode such as silicon oxide and an electrolyte solution. Light-controlled electrokinetic assembly of particles near surfaces relies on the combination of three functional elements: the AC electric field-induced assembly of planar aggregates; the patterning of the electrolyte/silicon oxide/silicon interface to exert spatial control over the assembly process; and the real-time control of the assembly process via external illumination. The present invention provides a set of fundamental operations enabling interactive control over the creation and placement of planar arrays of several types of particles and biomolecules and the manipulation of array shape and size. The present invention enables sample preparation and handling for diagnostic assays and biochemical analysis in an array format, and the functional integration of these operations. In addition, the present invention provides a procedure for the creation of material surfaces with desired properties and for the fabrication of surface-mounted optical components.

1 . A method for manipulating particles suspended at an interface between an electrode and an electrolyte solution, the method comprising the following steps: 
 generating an electric field at an interface between an electrode and an electrolyte solution;    patterning either the surface or interior of said electrode to modify its electrochemical properties; and    illuminating said surface with a predetermined light pattern to control the movement of said particles in accordance with said predetermined light pattern and the electrochemical properties of said electrode.    
     
     
         2 . The method of  claim 1 , wherein said electric field is at least one of a constant and a time varying electric field.  
     
     
         3 . The method of  claim 1 , wherein said patterning step is performed using at least one of UV-mediated oxide regrowth, surface chemical patterning and surface charge density profiling.  
     
     
         4 . The method of  claim 1 , wherein said electrode is a light sensitive electrode.  
     
     
         5 . The method of  claim 1 , wherein said illuminating step is performed using at least a single, spatially modulated light source.  
     
     
         6 . The method of  claim 1 , wherein the illuminating step comprises the further step of: 
 illuminating a selected area of said electrode to cause the particles to move into said selected area.    
     
     
         7 . The method of  claim 1 , wherein the illuminating step comprises the further step of: 
 illuminating a selected area of said electrode surface with a high intensity light pattern so as to cause the particles to move out of said selected area.    
     
     
         8 . The method of  claim 1 , wherein said illuminating step is time varying.  
     
     
         9 . The method of  claim 8 , wherein a traveling transverse constriction wave is established along said electrode.  
     
     
         10 . The method of  claim 1 , wherein the patterning step comprises the further step of: 
 creating a selected area of low impedance on said electrode to cause the particles to move into said selected area.    
     
     
         11 . The method of  claim 10 , wherein the frequency of said electric field is adjusted in order to place particles at the boundary delineating said area of low impedance.  
     
     
         12 . The method of  claim 1 , wherein the patterning step comprises the further step of: 
 providing said surface with low impedance except for a selected area to cause the particles to move out of said selected area.    
     
     
         13 . The method of  claim 1 , wherein said patterning step is used to create first and second areas of low impedance on said electrode, and said illuminating step is used to selectively connect said first and second areas to cause said particles to selectively move between said first area and said second area.  
     
     
         14 . The method of  claim 1 , wherein said patterning step is used to create first, second and third areas of low impedance on said surface, and said illuminating step is used to selectively cause said colloidal particles to move from said first and second areas into said third area.  
     
     
         15 . The met of  claim 1 , wherein said patterning step is used to create first, second and third areas of low impedance on said surface, and said illuminating step is used to selectively cause said particles to separate and move from said first area into said second and third areas.  
     
     
         16 . The method of  claim 1 , further comprising the following steps: 
 defining a pattern on said electrode, said pattern including a narrow conduit connected to a wide area; and    forming a substantially constant, reduced thickness oxide on said electrode, said reduced thickness oxide substantially corresponding to said narrow conduit and said wide area.    
     
     
         17 . The method of  claim 1 , further comprising the following steps: 
 defining a pattern on said electrode, said pattern including a narrow conduit; and    forming a variable thickness oxide on said electrode, said variable thickness oxide corresponding substantially to said narrow conduit and increasing from a first thickness at a first end of said narrow conduit to a second thickness at a second end of said narrow conduit.    
     
     
         18 . The method of  claim 17 , wherein said variable thickness oxide increases substantially linearly from said first thickness to said second thickness.  
     
     
         19 . A method of transverse electrokinetic movement of particles at an interface between an electrode and an electrolyte solution, the method comprising the following steps: 
 providing a light-sensitive electrode and an electrolyte solution;    generating an electric field at an interface between said electrode and said electrolyte solution; and    illuminating said electrode with a predetermined light pattern to form lateral gradients in the electrochemical properties of said electrode to control the movement of said particles in accordance with said illumination pattern in a direction substantially orthogonal to the direction of said electric field.    
     
     
         20 . A method of transverse electrokinetic movement of particles at an interface between an electrode and an electrolyte solution, the method comprising the following steps: 
 providing an electrode and an electrolyte solution;    generating an electric field at an interface between said electrode and said electrolyte solution; and    patterning said electrode to form lateral gradients in the electrochemical properties of said electrode to control the movement of said particles in accordance with said pattern created in said electrode in a direction substantially orthogonal to the direction of said electric field.    
     
     
         21 . A sorting apparatus for implementing the differential lateral displacement of particles suspended at an interface between an electrode and an electrolyte solution, said apparatus comprising: 
 an electric field generator which generates an electric field at said interface;    an electrode;    an electrolyte solution having a substantially continuous flow which effects the displacement of said particles in a direction substantially parallel to said interface;    said electrode being patterned and having its electrochemical properties modified;    an illumination source which illuminates said electrode with an adjustable, predetermined light pattern; and    a plurality of particles located in said electrolyte solution, said particles being acted upon by a combination of forces arising from said substantially continuous electrolyte flow and from said electric field in accordance with said predetermined light pattern and said electrode electrochemical properties, said particles being displaced in accordance with variations in the physical and chemical properties which determine the mobility of said particles.    
     
     
         22 . The sorting apparatus of  claim 21 , wherein said patterning includes a plurality of rows of intermittently spaced barrier areas of high impedance, the intermittent spacing of the barriers decreasing from one row to the next, said rows being positioned transversely across said electrode; 
 said electrode being further patterned to include an impedance profile characterized in that said impedance profile decreases in the direction across said electrode, said impedance profile having a high value at one side of said electrode corresponding to the row of barriers having the largest intermittent spacing, and a low value at an opposite side of said electrode corresponding to the row of barriers having the smallest intermittent spacing;    said electric field causing said particles to move in a direction substantially transverse to said electrolyte flow in accordance with said variation in impedance between said first and second sides of said electrode, said rows of intermittently spaced barriers acting to separate particles by size in accordance with the intermittent spacing of said rows of barriers.    
     
     
         23 . The sorting apparatus of  claim 21 , wherein said electrode is a light sensitive electrode.  
     
     
         24 . The sorting apparatus of  claim 21 , wherein said impedance profile is created by a predetermined illumination pattern.  
     
     
         25 . The sorting apparatus of  claim 21 , wherein: 
 said electrode patterning includes an area of low impedance bordered by an area of high impedance, said low impedance area including a narrow conduit in communication with a wide conduit, both said conduits being oriented parallel to the direction of said continuous flow of said electrolyte;    said wide conduit including a row of intermittently spaced areas of high impedance barriers traversing the width of said wide conduit;    a portion of said plurality of particles being optically distinguishable from the remaining particles;    a detector for visually inspecting said particles traversing the length of said narrow conduit in response to said continuous flow of electrolyte;    said illumination pattern being substantially in the shape of a rectangle having a longer dimension adjusted to be substantially equal to the width of said wide conduit, said rectangle having a smaller dimension which is adjusted to be substantially equivalent to the diameter of said particles, said pattern being located in front of said barriers, and said illumination pattern conforming to an intensity profile placing a maximal value of intensity in the center of said wide conduit and decreasing symmetrically to lower values of intensity at the two sides of said wide conduit; and    a delay activation circuit which activates said illumination profile in response to a signal derived from said visual inspection of said particles so as to cause an illuminated particle to be displaced from regions of maximum intensity to regions of lower intensity of said intensity profile and to be deflected into the intermittent spaces between said barriers.    
     
     
         26 . A method of dynamically assembling and disassembling an array of particles at an interface between an electrode and an electrolyte solution, the method comprising the following steps: 
 providing an electrode, an electrolyte solution and an interface therebetween;    providing a plurality of particles located in said electrolyte solution;    patterning said electrode to include at least one area of modified electrochemical properties;    illuminating said electrode with a predetermined light pattern;    generating an electric field at said interface to cause the assembly of an array of particles in accordance with the predetermined light pattern and the electrochemical properties of said electrode; and    removing said electric field to cause the disassembly of said array of particles.    
     
     
         27 . The method of  claim 26 , wherein said predetermined light pattern is adjusted to reconfigure said particle array in accordance with said predetermined light pattern.  
     
     
         28 . The method of  claim 26 , wherein said particle array is compositionally random and said particles are chemically encoded to include chemically or physically distinguishable characteristics.  
     
     
         29 . A method of forming a spatially encoded array including multiple types of particles suspended at an interface between an electrode and an electrolyte solution, said method comprising the following steps: 
 providing an electrode and an electrolyte solution;    providing multiple types of particles, each type being stored in accordance with chemically or physically distinguishable particle characteristics in one of a plurality of reservoirs, each reservoir containing a plurality of like-type particles suspended in said electrolyte solution;    providing said reservoirs in the form of an M×N grid arrangement;    patterning said electrode to define M×N compartments corresponding to said M×N grid of reservoirs;    depositing M×N droplets from said M×N reservoirs onto said corresponding M×N compartments, each said droplet originating from one of said reservoirs and remaining confined to one of said M×N compartments and each said droplet containing at least one particle;    positioning a top electrode above said droplets so as to simultaneously contact each said droplet;    generating an electric field between said top electrode and said M×N droplets;    using said electric field to form a particle array in each of said M×N compartments, each said particle array remaining spatially confined to one of said M×N droplets;    illuminating said M×N compartments on said patterned electrode with a predetermined light pattern to maintain the position of said particle arrays in accordance with said predetermined light pattern and the pattern of M×N compartments; and    positioning said top electrode closer to said electrode thereby fusing said M×N droplets into a continuous liquid phase, while maintaining each of said M×N particle arrays in one of the corresponding M×N compartments.    
     
     
         30 . The method of  claim 29 , wherein said compartments are hydrophilic and the remainder of said electrode surface is hydrophobic.  
     
     
         31 . A method of forming an optical lens array including particles suspended at an interface between an electrode and an electrolyte solution, said method comprising the following steps: 
 providing an electrode and an electrolyte solution having an interface therebetween;    providing a plurality of particles located in said electrolyte solution;    patterning said electrode to include at least one area of modified impedance; and    generating an electric field at said interface to cause said particles to assemble into an ordered array within said area of modified impedance.    
     
     
         32 . The method of  claim 31 , wherein said lens array is used to enhance light collection from said electrode surface.  
     
     
         33 . The method of  claim 31 , wherein said lens array acts to magnify the size and intensity of small particles underneath said lens array.  
     
     
         34 . The method of  claim 31 , wherein said lens array comprises large particles on the order of 10 microns in diameter and said small particles have a diameter on the order of 1 micron.  
     
     
         35 . A diffraction grating formed using particles suspended at an interface between an electrode and an electrolyte solution, said grating comprising: 
 an electrode and an electrolyte solution having an interface therebetween;    a plurality of particles located in said electrolyte solution, said particles including large particles and small particles;    said electrode being patterned to include at least one area of modified impedance; and    an electric field generator which generates an electric field at said interface causing said large and small particles to assemble into an array, said small particles being located between said large particles to create a large particle separation distance corresponding substantially to the size of said small particles, said large particle separation distance also determining the spatial frequency characteristics of said diffraction grating, said frequency characteristics being adjustable in dependence on the size of said small particles.    
     
     
         36 . An optical display formed using particles suspended at an interface between an electrolyte solution and an electrode, said display comprising: 
 an electrode and an electrolyte solution having an interface therebetween;    a plurality of particles located in said electrolyte solution, said particles including large particles and small particles;    said electrode being patterned to include at least one area of modified impedance;    an electric field generator which generates an electric field at said interface causing said large particles to assemble in accordance with the impedance of said patterned electrode, said electric field generator generating a time varying electric field causing said small particles to selectively move under said large particles to form an on-pixel, and also causing said small particles to selectively move away from said large particles to form an off-pixel in accordance with a selected frequency of said time varying electric field.    
     
     
         37 . A bioanalytical assay implemented using at least one array of particles, said particles being suspended at an interface between an electrode and an electrolyte solution, said assay comprising: 
 an electrode and an electrolyte solution therebetween;    a plurality of molecules located in said electrolyte, said molecules including a first type of molecule and a second type of molecule;    a biochemical protocol implementation unit which effects a biochemical interaction between said first and second types of molecules, said interaction resulting in the formation of paired entities, and said implementation unit operating to detect the formation of said paired entity;    plurality of particles located in said electrolyte solution;    an electric field generator which generates an electric field at said interface;    said electrode being patterned to include at least one area of modified electrochemical properties; and    an illumination source positioned to illuminate said surface with a predetermined light pattern to control the movement of said particles in accordance with said predetermined light pattern and the electrochemical properties of said electrode.    
     
     
         38 . A method of implementing a bioanalytical assay using at least one array of particles, said particles being suspended at an interface between an electrode and an electrolyte solution, said method comprising the following steps: 
 providing an electrode and an electrolyte solution therebetween;    providing a plurality of molecules, said molecules including a first type of molecule and a second type of molecule;    performing a biochemical protocol to effect the biochemical interaction between said first and second types of molecules, said interaction resulting in the formation of paired entities, said protocol including the additional step of detecting the formation of said paired entities;    providing a plurality of particles in said electrolyte solution;    generating an electric field at said interface;    patterning said electrode to include at least one area of modified electrochemical properties; and    illuminating said surface with a predetermined light pattern to control the movement of said particles in accordance with said predetermined light pattern and the electrochemical properties of said electrode.    
     
     
         39 . The method of  claim 38 , further comprising the step of marking individual distinguishable particles within said particle array by initiating a photochemical color-reaction in response to targeting said particles with a focused illumination source.  
     
     
         40 . The method of  claim 38 , further comprising the step of re-configuring said particle using interactive adjustments of said predetermined illumination pattern to isolate distinguishable particles within said array.  
     
     
         41 . The method of  claim 38 , further comprising the following steps: 
 providing a plurality of particles, each portion of said plurality having a plurality of a distinct type of molecule;    forming an array of said plurality of particles having said types of molecules, in accordance with said predetermined light pattern and the electrochemical properties of said electrode;    admitting a plurality of an additional type of molecule into said electrolyte solution under conditions favoring formation of paired entities with molecules on the surface of particles in said particle array; and    detecting the formation of paired entities on surfaces of a subset of particles assembled into said particle array, said paired entities thereby becoming distinguishable.    
     
     
         42 . The method of  claim 38 , further comprising the following steps: 
 providing a particle array including a plurality of types of particles, each type of particle having a plurality of a distinct type of molecule, said types of molecules being potentially capable of interacting with said molecules in solution to form paired entities;    providing said particles with a plurality of one type of molecule in said electrolyte solution under conditions favoring formation of paired entities with molecules on the surface of said particles;    forming an array of said particles in accordance with said predetermined light pattern and the electrochemical properties of said electrode, said particles having either an unpaired type of molecule or a paired entity, said paired entities rendering particular types of particles distinguishable; and    detecting said paired entities on surfaces of a portion of said particles assembled into said particle array.    
     
     
         43 . The method of  claim 38 , further comprising the following steps: 
 attaching a plurality of types of molecules to the surface of said particles, each said particle having a plurality of molecules of one type;    attaching a single distinct type of molecule to said electrode surface;    introducing a plurality of said particles having a plurality of types of molecules into said electrolyte solution;    forming an array of said particles in accordance with said predetermined light pattern and the electrochemical properties of said electrode surface under conditions favoring the biochemical interaction and formation of a paired entity between molecules on said particles and molecules on said electrode surface; and    disassembling said particle array, retaining and thereby selecting from the plurality of types of molecules initially introduced only those particles having specific types of molecules of demonstrated biochemical affinity for molecules on said electrode surface.    
     
     
         44 . The method of  claim 43 , wherein said particles include antibody-producing cells.  
     
     
         45 . The method of  claim 38 , further comprising the following steps: 
 attaching a plurality of types of molecules to the surface of said particles, each said particle having a plurality of molecules of one type;    attaching a single distinct type of biological target to said electrode surface;    introducing a plurality of said particles having a plurality of types of molecules into said electrolyte solution;    forming an array of said particles in accordance with said predetermined light pattern and the electrochemical properties of said electrode surface;    releasing molecules from said particles at a predetermined location by separating said molecules from said particles in response to a chemical or photochemical stimulus under conditions favoring the biochemical interaction and formation of paired entities between molecules released from said particles and biological targets displayed on said electrode surface; and    marking for identification such types of said particles having molecules which when released cause a detectable response in proximal biological targets.    
     
     
         46 . The method of  claim 45 , wherein said biological targets include cells grown in culture on said electrode, said cells being modified in a detectable way by exposure to said first type of molecules released from said particle array.  
     
     
         47 . The method of  claim 38 , further comprising the following steps: 
 placing the first and the second of said types of molecule in said electrolyte solution under conditions favoring the biochemical interaction and formation of paired entities of said molecules;    providing a plurality of said particles to capture said paired entities in solution; and    forming an array of said particles displaying said paired entity in accordance with said predetermined light pattern and the electrochemical properties of said electrode surface.    
     
     
         48 . The method of  claim 47 , wherein said particle capture is followed by the formation of a spatially encoded array of a plurality of types of distinct paired entities initially stored in a set of M×N distinct reservoirs of solution.  
     
     
         49 . The method of  claim 38 , wherein said paired entities include at least one of receptor-ligand, antibody-antigen and enzyme-substrate.  
     
     
         50 . The method of  claim 38 , wherein said paired entities include matching strands of oligonucleotides or strands of DNA or RNA, and formation of said paired entities involves hybridization.  
     
     
         51 . A method for performing multiple chemical and biochemical analytical procedures using at least one particle array, said method comprising the following steps: 
 providing an electrode and an electrolyte solution having an interface therebetween;    generating an electric field at an interface between an electrode and an electrolyte solution;    patterning said electrode to modify the electrochemical properties of said electrode;    illuminating said surface with a predetermined light pattern to control the movement of said particles in accordance with said predetermined light pattern and the electrochemical properties of said electrode;    performing a first procedure on a portion of said particles to produce a first reaction set of particles;    isolating said first reaction set of particles in accordance with said predetermined light pattern; and    performing a second procedure on said first reaction set of particles to produce a second reaction set of particles.    
     
     
         52 . The method of  claim 51 , wherein said performing and isolating steps are interactively controlled in real time by way of an adjustable illumination pattern.  
     
     
         53 . The method of  claim 51 , wherein said performing and isolating steps are dynamically reconfigurable.  
     
     
         54 . A method of manipulating nucleic acid, including DNA or RNA, comprising the following steps: 
 providing an electrode, an electrolyte solution and an interface therebetween;    providing a plurality of nucleic acid molecules in said electrolyte solution, said nucleic acid molecules being in a coiled configuration;    generating an electric field at said interface to cause the movement of said particles;    patterning said electrode to include areas of modified electrochemical properties which in conjunction with said electric field create controlled gradients in the flow velocity across the nucleic acid, said velocity gradient causing different portions of the nucleic acid to move at different velocities such that the nucleic acid is stretched in the direction of the local velocity gradient; and    maintaining a stagnation point of zero velocity such that the nucleic acid is substantially fixed in position.    
     
     
         55 . The method of  claim 54 , wherein said electrode is a light-sensitive electrode.  
     
     
         56 . The method of  claim 54 , wherein said velocity gradient and said stagnation point are created by a predetermined pattern of illumination.  
     
     
         57 . An apparatus for the manipulation of particles suspended at an interface between an electrode and an electrolyte solution, said apparatus comprising: 
 an electrode and an electrolyte solution;    an electric field generator for generating an electric field at an interface between said electrode and said electrolyte solution;    said surface or interior of said electrode being patterned to modify its electrochemical properties; and    an illumination source which illuminates said surface with a predetermined light pattern to control the movement of said particles in accordance with said predetermined light pattern and the electrochemical properties of said electrode.    
     
     
         58 . An apparatus for the transverse electrokinetic movement of particles at an interface between an electrode and an electrolyte solution, said apparatus comprising: 
 a light-sensitive electrode and an electrolyte solution;    an electric field generator which generates an electric field at an interface between said electrode and said electrolyte solution; and    an illumination source which illuminates said electrode with a predetermined light pattern to form lateral gradients in the electrochemical properties of said electrode to control the movement of said particles in accordance with said illumination pattern in a direction substantially orthogonal to the direction of said electric field.    
     
     
         59 . A sorting method for implementing the differential lateral displacement of particles suspended at an interface between an electrode and an electrolyte solution, said method comprising the following steps: 
 providing an electrode;    providing an electrolyte solution having a substantially continuous flow which effects the displacement of said particles in a direction substantially parallel to said interface;    generating an electric field at said interface;    patterning said electrode in order to modify its electrochemical properties;    illuminating said electrode with an adjustable, predetermined light pattern; and    providing a plurality of particles located in said electrolyte solution, said particles being acted upon by a combination of forces arising from said substantially continuous electrolyte flow and from said electric field in accordance with said predetermined light pattern and said electrode electrochemical properties, said particles being displaced in accordance with variations in the physical and chemical properties which determine the mobility of said particles.    
     
     
         60 . An apparatus for dynamically assembling and disassembling an array of particles at an interface between an electrode and an electrolyte solution, said apparatus comprising: 
 an electrode, an electrolyte solution and an interface therebetween;    a plurality of particles located in said electrolyte solution;    said electrode being patterned to include at least one area of modified electrochemical properties;    an illumination source which illuminates said electrode with a predetermined light pattern;    an electric field generator which generates an electric field at said interface to cause the assembly of an array of particles in accordance with the predetermined light pattern and the electrochemical properties of said electrode; and    an electric field removal unit which removes said electric field to cause the disassembly of said array of particles.    
     
     
         61 . An apparatus for forming a spatially encoded array including multiple types of particles suspended at an interface between an electrode and an electrolyte solution, said apparatus comprising: 
 an electrode and an electrolyte solution;    multiple types of particles, each type being stored in accordance with chemically or physically distinguishable particle characteristics in one of a plurality of reservoirs, each reservoir containing a plurality of like-type particles suspended in said electrolyte solution;    said reservoirs being arranged in the form of an M×N grid arrangement;    said electrode being patterned to define M×N compartments corresponding to said M×N grid of reservoirs;    M×N droplets which are deposited from said M×N reservoirs onto said corresponding M×N compartments, each said droplet originating from one of said reservoirs and remaining confined to one of said M×N compartments and each said droplet containing at least one particle;    a top electrode positioned above said droplets so as to simultaneously contact each said droplet;    an electric field generator which generates an electric field between said top electrode and said M×N droplets;    said electric field being used to form a particle array in each of said M×N compartments, each said particle array remaining spatially confined to one of said M×N droplets;    an illumination source which illuminates said M×N compartments on said patterned electrode with a predetermined light pattern to maintain the position of said particle arrays in accordance with said predetermined light pattern and the pattern of M×N compartments; and    said top electrode being positioned closer to said electrode thereby fusing said M×N droplets into a continuous liquid phase, while maintaining each of said M×N particle arrays in one of the corresponding M×N compartments.    
     
     
         62 . An optical lens array including particles suspended at an interface between an electrode and an electrolyte solution, said lens array comprising: 
 an electrode and an electrolyte solution having an interface therebetween;    a plurality of particles located in said electrolyte solution;    said electrode being patterned to include at least one area of modified impedance; and    an electric field generator which generates an electric field at said interface to cause said particles to assemble into an ordered array within said area of modified impedance.    
     
     
         63 . A method for forming a diffraction grating using particles suspended at an interface between an electrode and an electrolyte solution, said method comprising the following steps: 
 providing an electrode and an electrolyte solution having an interface therebetween;    providing a plurality of particles located in said electrolyte solution, said particles including large particles and small particles;    patterning said electrode to include at least one area of modified impedance; and    generating an electric field at said interface to cause said large and small particles to assemble into an array, said small particles being located between said large particles to create a large particle separation distance corresponding substantially to the size of said small particles, said large particle separation distance also determining the spatial frequency characteristics of said diffraction grating, said frequency characteristics being adjustable in dependence on the size of said small particles.    
     
     
         64 . A method for forming an optical display using particles suspended at an interface between an electrolyte solution and an electrode, said method comprising the following steps: 
 providing an electrode and an electrolyte solution having an interface therebetween;    providing a plurality of particles located in said electrolyte solution, said particles including large particles and small particles;    patterning said electrode to include at least one area of modified impedance;    generating an electric field at said interface causing said large particles to assemble in accordance with the impedance of said patterned electrode, said electric field generator generating a time varying electric field causing said small particles to selectively move under said large particles to form an on-pixel, and also causing said small particles to selectively move away from said large particles to form an off-pixel in accordance with a selected frequency of said time varying electric field.    
     
     
         65 . An apparatus for performing multiple chemical and biochemical analytical procedures using at least one particle array, said apparatus comprising: 
 an electrode and an electrolyte solution having an interface therebetween;    an electric field generator which generates an electric field at an interface between an electrode and an electrolyte solution;    said electrode being patterned to modify the electrochemical properties of said electrode;    an illuminating source which illuminates said surface with a predetermined light pattern to control the movement of said particles in accordance with said predetermined light pattern and the electrochemical properties of said electrode;    means for performing a first procedure on a portion of said particles to produce a first reaction set of particles;    means for isolating said first reaction set of particles in accordance with said predetermined light pattern; and    means for performing a second procedure on said first reaction set of particles to produce a second reaction set of particles.    
     
     
         66 . An apparatus for manipulating nucleic acid, including DNA or RNA, said apparatus comprising: 
 an electrode, an electrolyte solution and an interface therebetween;    a plurality of nucleic acid molecules in said electrolyte solution, said nucleic acid molecules being in a coiled configuration;    an electric field generator which generates an electric field at said interface to cause the movement of said particles; and    said electrode being patterned to include areas of modified electrochemical properties which in conjunction with said electric field create controlled gradients in the flow velocity across the nucleic acid, said velocity gradient causing different portions of the nucleic acid to move at different velocities such that the nucleic acid is stretched in the direction of the local velocity gradient, wherein a stagnation point of zero velocity is maintained such that the nucleic acid is substantially fixed in position.